Chapter 11 CELL COMMUNICATION - HCC Learning Web

Chapter 11:

CELL COMMUNICATION

Evelyn I. Milian

Instructor

2012

BIOLOGY I

BIOLOGY I. Chapter 11 – Cell Communication

Why is cell-to-cell communication important?

• Communication between cells is important for multicellular organisms as well as for unicellular organisms.

• Cells communicate with each other to coordinate their activities in a way that enables an organism to develop, survive and reproduce.

– Share nutrients, ions, etc.

– Influence other cells through signals

– Interact to work together in tissues and organs (e.g. the heart, the muscles)

2 Evelyn I . Mil ian - Instructor


Evolution of Cell Signaling

• Signal transduction pathway:

the process by which a signal on

a cell’s surface is converted into a

specific cellular response.

• Cell signaling (signal transduction)

in microbes (such as yeast, a type

of fungus) has much in common

with processes in multicellular

organisms, including animals,

suggesting an early origin of

signaling mechanisms.

Evelyn I . Mil ian - Instructor 3


Local and Long Distance Signaling

1. Cell communication by direct contact between cells:

– Cell junctions: allow molecules to pass freely between adjacent cells.

• Gap junctions,

plasmodesmata, etc.

– Cell-cell recognition: cells communicate by interaction between cell surface molecules.

• Very important in such

processes as embryonic

development and immune

responses.




2. Cell communication by indirect contact through messenger molecules:

a) Paracrine signaling = local regulators released by a secreting cell travel only short distances to influence neighboring cells.

• Example: growth factors.

b) Synaptic signaling = neurotransmitters released by a nerve cell stimulate a target cell.

• The neurotransmitter is

released into the synapse,

the space between the

nerve cell and its target cell.


A nerve signal can travel along a

series of nerve cells, some of which

can be quite long; therefore, it can also

be considered long-distance signaling.



c) Endocrine (hormonal) signaling = chemicals called hormones are released by specialized endocrine cells into blood vessels.

– The hormones may travel long

distances to other parts of the body.

– Insulin, a hormone that regulates

sugar levels in blood, is an example

of a mammalian hormone.



The Three Stages of Cell Signaling (Communication): Overview

• From the perspective of the cell receiving the message, the process of cell signaling can be divided into three stages:

1) Reception: The target cell’s detection of a signal molecule (ligand) from outside the cell, when it binds to a receptor protein.

2) Transduction: The conversion of a signal from outside the cell to a form that can bring about a specific cellular response.

3) Response: The change in a specific cellular activity brought about by a transduced signal from outside the cell.

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Cell Signaling (Communication): (1) Reception

• In reception, a signal molecule, called a ligand, binds to a receptor protein (located on the cell’s surface or inside the cell) causing it to change its shape (conformation).

– * This binding is highly specific.

– * Most signal receptors are plasma membrane proteins. However, some signal receptors are intracellular (located inside the cell, in the cytoplasm or the nucleus).



Intracellular Receptors


• Intracellular receptors are

cytoplasmic or nuclear

proteins.

• Signal molecules that are

small enough or hydrophobic

enough and can readily cross

the plasma membrane use

these receptors.

– Examples include: steroid

hormones (such as

testosterone) and thyroid

hormones.


Receptors in the Plasma Membrane

• Most water-soluble signaling molecules, generally too

large to pass freely through the plasma membrane, bind

to specific sites on receptor proteins embedded in the

plasma membrane of the cell.

• The specific ligand binds to the receptor on the plasma

membrane and the receptor either changes shape or

aggregates.

• Three major types of plasma membrane receptors are:

– G-protein-coupled receptors

– Receptor tyrosine kinases

– Ion channel receptors



Receptors in the Plasma Membrane: G-Protein-Coupled Receptors

• A G-protein-coupled

receptor is a membrane

receptor that works with

the help of a cytoplasmic

G protein, which binds

the energy-rich molecule

GTP (guanosine

triphosphate).

• Ligand binding activates

the receptor, which then

activates a specific G

protein, which activates

yet another protein, thus

propagating the signal

along a signal

transduction pathway.


G-protein-linked receptors are widespread in organisms and diverse in their functions, including roles in sensory reception. They are also involved in many human diseases, including bacterial infections.


Receptors in the Plasma Membrane: Receptor Tyrosine Kinases

• Receptor tyrosine kinases have enzymatic activity and react to the binding of signal molecules by forming dimers and then adding phosphate groups to tyrosines on the cytoplasmic side of the other subunit of the dimer.

• Relay proteins in the cell can then be activated by binding to different phosphorylated tyrosines, allowing this receptor to trigger several pathways at once. These receptors are involved in cell growth and reproduction.

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A tyrosine kinase is an enzyme that catalyzes the transfer of a phosphate group from ATP to the amino acid tyrosine on a substrate protein.

Evelyn I . Mil ian - Instructor


Receptors in the Plasma Membrane:

Ion Channel Receptors

• A ligand-gated ion channel receptor in a

membrane opens or closes when a specific

signal molecule binds to the receptor

protein, regulating the flow of specific ions.

• These receptors have a region that can act

as a “gate” when the receptor changes

shape upon binding of the ligand. The gate

opens or closes, allowing or blocking the

flow of specific ions, such as Na+ or Ca2+

through a channel in the receptor.



Cell Signaling (Communication): (2) Transduction

• Transduction is the conversion of a signal from outside the cell to a form that can bring about a specific cellular response.

– It is initiated when the binding of the signaling molecule changes the receptor protein in some way.

• Transduction often occurs through a sequence of changes requiring different relay molecules—a signal transduction pathway.

– Cascades of molecular interactions relay signals from receptors to target molecules in the cell.

– At each step in a pathway, the signal is transduced into a different form, commonly a conformational change in a protein.

• Advantage of multistep pathways:

– Greatly amplifying a signal (and thus producing a large cellular response), more opportunities for coordination and regulation.




• Phosphorylation and dephosphorylation of proteins is a widespread cellular mechanism for regulating protein activity.

– Phosphorylation: The addition of a phosphate group to a protein or another molecule.

• Many signal transduction pathways include “phosphorylation

cascades”; a series of enzymes called protein kinases each

transfer a phosphate group (from ATP) to the next protein in line,

activating it.

– Dephosphorylation: The removal of a phosphate group.

• Enzymes called protein phosphatases rapidly remove the

phosphates from the proteins kinases, making them inactive and

available for reuse (turning off the signal transduction pathway

when the initial signal is no longer present).






• Small Molecules and Ions as Second Messengers

– In addition to proteins (kinases, phosphatases), signal transduction pathways may involve small nonprotein water-soluble molecules or ions called second messengers (the “first messenger” is the extracellular signal molecule that binds to the membrane receptor).

– Second messengers, diffuse readily through the cell and thus help broadcast signals quickly.

– Examples: cyclic AMP (cAMP) and calcium ions (Ca2+).



Small Molecules and Ions as Second Messengers

• Cyclic AMP (cyclic adenosine

monophosphate)

– The first messenger

activates a G-protein-linked

receptor, which activates a

specific G protein.

– In turn, the G protein

activates adenylyl cyclase,

an enzyme embedded in the

plasma membrane, which

converts ATP to cAMP.

– The cAMP then activates

another protein.




• Calcium Ions (Ca2+)

– Many signal molecules in

animals (e.g. neurotransmitters,

growth factors, some hormones),

induce responses in their target

cells via signal transduction

pathways that increase the

cytosolic concentration of Ca2+.

This causes many responses in

animal cells, such as muscle cell

contraction, secretion of certain

substances, and cell division.

– Cells use Ca2+ as a second

messenger in both G-protein

and tyrosine kinase pathways.


Figure 11.11. The maintenance of Ca2+

concentration in an animal cell. The Ca2+ concentration in the cytosol is usually much lower than in the extracellular fluid and ER.



• Calcium Ions (Ca2+) and Inositol Trisphosphate (IP3)

– In response to a signal

relayed by a signal

transduction pathway, the

cytosolic calcium level may

rise, usually by a mechanism

that releases Ca2+ from the

cell’s endoplasmic reticulum.

– Calcium release in the cell

involves two other second

messengers, IP3 and DAG

(diacylglycerol). DAG

functions as a second

messenger in other pathways.



Cell Signaling (Communication): (3) Response

• Signal transduction ultimately triggers a cellular response,

leading to the regulation of one or more cellular activities.

• Cytoplasmic and Nuclear Responses

– In the cytoplasm: Enzyme activity, rearrangement of the

cytoskeleton, protein synthesis, protein activity, and many

other activities are regulated.

– In the nucleus: Activation or inactivation of specific genes,

by transcription factors (special proteins that control which

genes are turned on in a particular cell at a particular time).



Cell Signaling (Communication): (3) Response in the Cytoplasm or the Nucleus



Cell Signaling (Communication):

Fine-Tuning of the Response

• Signal Amplification

– One of the benefits of multistep

signaling pathways is signal

amplification: each catalytic protein

in a signaling pathway amplifies the

signal by activating multiple copies of

the next component of the pathway.

• The Specificity of Cell Signaling and Coordination of the Response

– The particular collection of proteins in

a cell gives the cell great specificity in

both the signals it detects and the

responses it carries out.



Cell Signaling (Communication): Fine-Tuning of the Response

• Signaling Efficiency: Scaffolding Proteins and Signaling Complexes

– Scaffolding proteins are large relay proteins to which several other

relay proteins are simultaneously attached to increase the efficiency of

signal transduction.

– In this figure, the scaffolding protein simultaneously binds to a specific

activated membrane receptor and three different protein kinases. This

physical arrangement facilitates signal transduction by these molecules.

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Cell Signaling (Communication):

Fine-Tuning of the Response

• Termination of the Signal

– If a signaling pathway component becomes locked into one

state, whether active or inactive, dire consequences for the

organism can result, therefore, the changes that signals

produce are reversible.

– Signal response is terminated quickly by the reversal of

ligand binding. When signal molecules leave the receptor,

the receptor reverts to its inactive form and relay molecules

are inactivated.

– In this way, the cell is soon ready to respond to a new signal.



The Three Stages of Cell Signaling: An Analogy

Cells Analogy

Reception The target cell’s detection of a

signal molecule from outside

the cell, when it binds to a

receptor protein.

A TV camera (receptor)

is shooting a scene.

Transduction The conversion of a signal

from outside the cell to a form

that can bring about a specific

cellular response.

The picture is converted

to electrical signals

(transduction pathway)

that are understood by

the TV in your house.

Response The change in a specific

cellular activity brought about

by a transduced signal from

outside the cell.

The electrical signals are

converted to a picture on

your TV screen (the

response).





28 Evelyn I . Mil ian - Instructor


References

• Audesirk, Teresa; Audesirk, Gerald & Byers, Bruce E. (2005). Biology: Life on Earth. Seventh Edition. Pearson Education, Inc.-Prentice Hall. NJ, USA.

• Brooker, Robert J.; Widmaier, Eric P.; Graham, Linda E.; Stiling, Peter D. (2008). Biology. The McGraw-Hill Companies, Inc. NY, USA.

• Campbell, Neil A.; Reece, Jane B., et al. (2011). Biology. Ninth Edition. Pearson Education, Inc.-Pearson Benjamin Cummings. CA, USA.

• Ireland, K.A. (2011). Visualizing Human Biology. Second Edition. John Wiley & Sons, Inc. NJ, USA.

• Mader, Sylvia S. (2010). Biology. Tenth Edition. The McGraw-Hill Companies, Inc. NY, USA.

• Martini, Frederic H.; Nath, Judi L. (2009). Fundamentals of Anatomy & Physiology. Eighth Edition. Pearson Education, Inc. – Pearson Benjamin Cummings. CA, USA.

• Solomon, Eldra; Berg, Linda; Martin, Diana W. (2008). Biology. Eighth Edition. Cengage Learning. OH, USA.

• Starr, Cecie. (2008). Biology: Concepts and Applications , Volume I. Thompson Brooks/Cole. OH, USA.

• Tortora, Gerard J.; Derrickson, Bryan. (2006). Principles of Anatomy and Physiology. Eleventh Edition. John Wiley & Sons, Inc. NJ, USA. www.wiley.com/college/apcentral.


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Chapter 11 CELL COMMUNICATION - HCC Learning Web